Rapid expulsion is an IgE or IgG-mediated intestinal immune response that results in the elimination from the gut of large number os T. spiralis muscle larvae in a challenge infection of actively immune rats. This immune response has several unique characteristics that are of general significance. To wit: it is the only native IgE-mediated anti nematode immune response for which the cellular and molecular components have been defined. Furthermore, it is the only unequivocal example of a host- protective function for IgE in a normal immune response. Analysis of this response is therefore fundamentally relevant not just to mechanisms of immunity to nematodes but also to allergy and to intestinal immunity. During the tenure of this grant we defined the site of production, the kinetics, migration pattern and phenotype of protective cells which will transfer rapid expulsion provided CD4+ CD45RC- cells have first been transferred. The role of CD4+ OX22 cells can be substituted by infecting rats with an unrelated nematode. Heligmosomoides polygyrus, 5- understanding of anti nematode immunity. We propose herein to continue these studies with a focus on the properties of the protective cells and IgE, the two known essential elements. What is not known is how the cells and IgE interact to result in the expression of rapid expulsion. We therefore will determine the behavior and function of both cells and IgE in vivo and define the precise mechanism through which rapid expulsion is expressed. The work will involve cellular and molecular studies in vitro and in vivo. We have also recently developed an afferent/efferent lymph and serum assay system with which we can measure local, regional and specifically remove cytokines and other effectors. We will use antisense oligonucleotide therapy to specifically remove cytokine production ability from CD4+ OX22 cells, prior to transfer, to determine which cytokines are essential for cellular function. This will be backed by an analysis of the cytokine profile of labelled CD4+ OX22 cells isolated from the gut after transfer to naive animals. Furthermore, we have shown that infection. CD4+ OX22 cells and IL-4 can all elevate the IgE-binding and transport properties of the gut. We have demonstrated the upregulation of IgE binding molecules on lamina propria cells and intraepithelial lymphocytes and will identify and characterize FceR and the cells bearing them. We will search for effector molecules in afferent lymph from actively immune and adoptively transferred rats during expression of rapid expulsion and isolate active molecules. This approach is focussed, integrated and will define effectors in a physiologically relevant manner. Abbreviations: T. spiralis, Ts; intraepithelial lymphocytes, IEL; lamina propria, LP, enterocyte, ENT; thoracic duct, TD. Rapid expulsion, RE: muscle larvae ML.